Exploring the Genomic Architectures of Health, Physical Traits and Antisocial Behavioral Outcomes: A Brief Report

© Copyright © 2020 Tielbeek and Boutwell. A widely replicated finding across the behavioral sciences is that antisocial behaviors correlate with an array of health problems. Less clear, however, is the precise nature of this association. There is reason to suspect that a direct causal link exists between incarceration—a consequence of some antisocial behaviors—and certain negative health outcomes, for instance. However, it might be the case that broader phenotypes like antisocial behavior may correlate with certain health and physiological traits at a genomic level. We explore this possibility from a theoretical vantage point, while also presenting some preliminary data from existing secondary sources. Tentatively, no significant genetic correlations emerged across a host of health, physiological, and wellbeing outcomes after correction for multiple testing. However, more work is needed exploring this topic. We propose that future studies should make use of larger, more diverse samples and examine the genetic overlap between homogeneous clusters of antisocial behavioral subtypes and disease traits or symptoms

Shared genomic architectures of COVID-19 and antisocial behavior

Little is known about the genetics of norm violation and aggression in relation to coronavirus disease 2019 (COVID-19). To investigate this, we used summary statistics from genome-wide association studies and linkage disequilibrium score regression to calculate a matrix of genetic correlations (rgs) for antisocial behavior (ASB), COVID-19, and various health and behavioral traits. After false-discovery rate correction, ASB was genetically correlated with COVID-19 (rg = 0.51; P = 1.54E-02) and 19 other traits. ASB and COVID-19 were both positively genetically correlated with having a noisy workplace, doing heavy manual labor, chronic obstructive pulmonary disease, and genitourinary diseases. ASB and COVID-19 were both inversely genetically correlated with average income, education years, healthspan, verbal reasoning, lifespan, cheese intake, and being breastfed as a baby. But keep in mind that rgs are not necessarily causal. And, if causal, their prevailing directions of effect (which causes which) are indiscernible from rgs alone. Moreover, the SNP-heritability (hg2) estimates for two measures of COVID-19 were very small, restricting the overlap of genetic variance in absolute terms between ASB and COVID-19. Nonetheless, our findings suggest that those with antisocial tendencies possibly have a higher risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than those without antisocial tendencies. This may have been especially true early in the pandemic before vaccines against SARS-CoV-2 were available and before the emergence of the highly transmissible Omicron variant

Analisa Pembayaran Pajak Dan Persepsi Penghasilan Menurut Wajib Pajak Orang Pribadi Yang Membayar Persepuluhan

Penelitian ini bertujuan untuk mengetahui persepsi penghasilan menurut Wajib Pajak Orang Pribadi yang membayar persepuluhan. Penelitian ini dilakukan dengan melihat definisi penghasilan menurut Wajib Pajak melalui pembayaran persepuluhan yang dilakukannya, karena pembayaran persepuluhan didasari oleh pemikiran masing-masing individu terkait apa saja yang termasuk dalam penghasilan (self-defined income). Jumlah responden yang digunakan dalam penelitian ini adalah 30 Wajib Pajak Orang Pribadi di Surabaya yang menganut agama Kristen. Teknik analisa yang digunakan adalah metode sequential explanatory design, yang diawali dengan analisa kuantitatif menggunakan Uji Beda Dua Kelompok dan kemudian dilanjutkan dengan analisa kualitatif.Hasil penelitian menunjukkan bahwa Wajib Pajak cenderung memiliki persepsi bahwa yang termasuk dalam definisi penghasilan adalah penerimaan kas, yang diukur dengan jumlah total kas yang diterima dalam suatu periode tertentu. Kemudian juga ditemukan bahwa tidak terdapat perbedaan antara pembayaran persepuluhan yang dilakukan oleh Wajib Pajak dengan pembayaran Pajak Penghasilan, yang artinya bahwa perilaku pembayaran Pajak Penghasilan dilakukan sesuai dengan persepsi penghasilan menurut Wajib Pajak. Dari analisa kualitatif dalam penelitian ini, ditemukan bahwa persepsi Wajib Pajak terkait dengan praktek perpajakan di Indonesia juga berperan dalam pembayaran pajak yang dilakukan oleh Wajib Pajak

Exploring the genetic correlations of antisocial behaviour and life history traits.

UNLABELLED: Prior evolutionary theory provided reason to suspect that measures of development and reproduction would be correlated with antisocial behaviours in human and non-human species. Behavioural genetics has revealed that most quantitative traits are heritable, suggesting that these phenotypic correlations may share genetic aetiologies. We use genome-wide association study data to estimate the genetic correlations between various measures of reproductive development (N = 52 776-318 863) and antisocial behaviour (N = 31 968). Our genetic correlation analyses demonstrate that alleles associated with higher reproductive output (number of children ever born, r g = 0.50, P = 0.0065) were positively correlated with alleles associated with antisocial behaviour, whereas alleles associated with more delayed reproductive onset (age at first birth, r g = -0.64, P = 0.0008) were negatively associated with alleles linked to antisocial behaviour. Ultimately, these findings coalesce with evolutionary theories suggesting that increased antisocial behaviours may partly represent a faster life history approach, which may be significantly calibrated by genes. DECLARATION OF INTEREST: None

Resting heart rate and antisocial behaviour: a Mendelian randomisation study

Observational studies frequently report phenotypic associations between low resting heart rate (RHR) and higher levels of antisocial behaviour (ASB), although it remains unclear whether this relationship reflects causality. To triangulate evidence, we conducted two-sample univariable Mendelian randomisation (MR), multivariable MR and linkage disequilibrium score regression (LDSC) analyses. Genetic data were accessed from published genome-wide association studies (GWAS) for RHR (n = 458,835) and ASB (n = 85,359) for the univariable analyses, along with a third GWAS for heart rate variability (HRV; n = 53,174) for all other analyses. Genome-wide significant (p < 5 × 10-8) single-nucleotide polymorphisms associated with RHR (n = 278) were selected as instrumental variables and the outcome was a composite measure of ASB. No causal association was observed between RHR and ASB (BIVW =  - 0.0004, p = 0.841). The multivariable MR analyses including RHR and HRV also suggested no causal associations (BIVW = 0.016, p = 0.914) and no genetic correlations between the heart rate measures and ASB were observed using LDSC (rg = 0.057, p = 0.169). Sensitivity analyses suggested that our results are not likely to be affected by heterogeneity, pleiotropic effects, or reverse causation. These findings suggest that individual differences in autonomic nervous system functioning indexed by RHR are not likely to directly contribute to the development of ASB. Therefore, previously observed associations between RHR and ASB may arise from confounding, reverse causation, and/or additional study characteristics. Further causally informative longitudinal research is required to confirm our findings, and caution should be applied when using measures of RHR in interventions targeting ASB

Semiautomatic Assessment of the Terminal Ileum and Colon in Patients with Crohn Disease Using MRI (the VIGOR++ Project)

Rationale and Objectives: The objective of this study was to develop and validate a predictive magnetic resonance imaging (MRI) activity score for ileocolonic Crohn disease activity based on both subjective and semiautomatic MRI features. Materials and Methods: An MRI activity score (the “virtual gastrointestinal tract [VIGOR]” score) was developed from 27 validated magnetic resonance enterography datasets, including subjective radiologist observation of mural T2 signal and semiautomatic measurements of bowel wall thickness, excess volume, and dynamic contrast enhancement (initial slope of increase). A second subjective score was developed based on only radiologist observations. For validation, two observers applied both scores and three existing scores to a prospective dataset of 106 patients (59 women, median age 33) with known Crohn disease, using the endoscopic Crohn's Disease Endoscopic Index of Severity (CDEIS) as a reference standard. Results: The VIGOR score (17.1 × initial slope of increase + 0.2 × excess volume + 2.3 × mural T2) and other activity scores all had comparable correlation to the CDEIS scores (observer 1: r = 0.58 and 0.59, and observer 2: r = 0.34–0.40 and 0.43–0.51, respectively). The VIGOR score, however, improved interobserver agreement compared to the other activity scores (intraclass correlation coefficient = 0.81 vs 0.44–0.59). A diagnostic accuracy of 80%–81% was seen for the VIGOR score, similar to the other scores. Conclusions: The VIGOR score achieves comparable accuracy to conventional MRI activity scores, but with significantly improved reproducibility, favoring its use for disease monitoring and therapy evaluation

ECCO-ESGAR Topical Review on Optimizing Reporting for Cross-Sectional Imaging in IBD

Background and Aims: Diagnosis and follow up of patients with inflammatory bowel disease [IBD] requires cross-sectional imaging modalities, such as intestinal ultrasound [IUS], magnetic resonance imaging [MRI], and computed tomography [CT]. The quality and homogeneity of medical reporting are crucial to ensure effective communication between specialists and to improve patient care. The current topical review addresses optimized reporting requirements for cross-sectional imaging in IBD. // Methods: An expert consensus panel consisting of gastroenterologists, radiologists, and surgeons convened by the ECCO in collaboration with ESGAR performed a systematic literature review covering the reporting aspects of MRI, CT, IUS, endoanal ultrasonography, and transperineal ultrasonography in IBD. Practice position statements were developed utilizing a Delphi methodology incorporating two consecutive rounds. Current practice positions were set when ≥80% of the participants agreed on a recommendation. // Results: Twenty-five practice positions were developed, establishing standard terminology for optimal reporting in cross-sectional imaging. Assessment of inflammation, complications, and imaging of perianal CD are outlined. The minimum requirements of a standardized report, including a list of essential reporting items, have been defined. // Conclusions: This topical review offers practice recommendations to optimize and homogenize reporting in cross-sectional imaging in IBD

Elevated acute phase proteins affect pharmacokinetics in COVID-19 trials: Lessons from the CounterCOVID - imatinib study.

This study aimed to determine whether published pharmacokinetic (PK) models can adequately predict the PK profile of imatinib in a new indication, such as coronavirus disease 2019 (COVID-19). Total (bound + unbound) and unbound imatinib plasma concentrations obtained from 134 patients with COVID-19 participating in the CounterCovid study and from an historical dataset of 20 patients with gastrointestinal stromal tumor (GIST) and 85 patients with chronic myeloid leukemia (CML) were compared. Total imatinib area under the concentration time curve (AUC), maximum concentration (C &lt;sub&gt;max&lt;/sub&gt; ) and trough concentration (C &lt;sub&gt;trough&lt;/sub&gt; ) were 2.32-fold (95% confidence interval [CI] 1.34-3.29), 2.31-fold (95% CI 1.33-3.29), and 2.32-fold (95% CI 1.11-3.53) lower, respectively, for patients with CML/GIST compared with patients with COVID-19, whereas unbound concentrations were comparable among groups. Inclusion of alpha1-acid glycoprotein (AAG) concentrations measured in patients with COVID-19 into a previously published model developed to predict free imatinib concentrations in patients with GIST using total imatinib and plasma AAG concentration measurements (AAG-PK-Model) gave an estimated mean (SD) prediction error (PE) of -20% (31%) for total and -7.0% (56%) for unbound concentrations. Further covariate modeling with this combined dataset showed that in addition to AAG; age, bodyweight, albumin, CRP, and intensive care unit admission were predictive of total imatinib oral clearance. In conclusion, high total and unaltered unbound concentrations of imatinib in COVID-19 compared to CML/GIST were a result of variability in acute phase proteins. This is a textbook example of how failure to take into account differences in plasma protein binding and the unbound fraction when interpreting PK of highly protein bound drugs, such as imatinib, could lead to selection of a dose with suboptimal efficacy in patients with COVID-19

Polygenic risk scores and brain structures both contribute to externalizing behavior in childhood: a study in the Adolescent Brain and Cognitive Development (ABCD) cohort

Pathways through Adolescenc

Vertebroplasty versus sham procedure for painful acute osteoporotic vertebral compression fractures (VERTOS IV):Randomised sham controlled clinical trial

Objective To assess whether percutaneous vertebroplasty results in more pain relief than a sham procedure in patients with acute osteoporotic compression fractures of the vertebral body. Design Randomised, double blind, sham controlled clinical trial. Setting Four community hospitals in the Netherlands, 2011-15. Participants 180 participants requiring treatment for acute osteoporotic vertebral compression fractures were randomised to either vertebroplasty (n=91) or a sham procedure (n=89). Interventions Participants received local subcutaneous lidocaine (lignocaine) and bupivacaine at each pedicle. The vertebroplasty group also received cementation, which was simulated in the sham procedure group. Main outcome measures Main outcome measure was mean reduction in visual analogue scale (VAS) scores at one day, one week, and one, three, six, and 12 months. Clinically significant pain relief was defined as a decrease of 1.5 points in VAS scores from baseline. Secondary outcome measures were the differences between groups for changes in the quality of life for osteoporosis and Roland-Morris disability questionnaire scores during 12 months’ follow-up. Results The mean reduction in VAS score was statistically significant in the vertebroplasty and sham procedure groups at all follow-up points after the procedure compared with baseline. The mean difference in VAS scores between groups was 0.20 (95% confidence interval −0.53 to 0.94) at baseline, −0.43 (−1.17 to 0.31) at one day, −0.11 (−0.85 to 0.63) at one week, 0.41 (−0.33 to 1.15) at one month, 0.21 (−0.54 to 0.96) at three months, 0.39 (−0.37 to 1.15) at six months, and 0.45 (−0.37 to 1.24) at 12 months. These changes in VAS scores did not, however, differ statistically significantly between the groups during 12 months’ follow-up. The results for secondary outcomes were not statistically significant. Use of analgesics (non-opioids, weak opioids, strong opioids) decreased statistically significantly in both groups at all time points, with no statistically significant differences between groups. Two adverse events occurred in the vertebroplasty group: one respiratory insufficiency and one vasovagal reaction. Conclusions Percutaneous vertebroplasty did not result in statistically significantly greater pain relief than a sham procedure during 12 months’ follow-up among patients with acute osteoporotic vertebral compression fractures